Persistent post-surgical pain and neuropathic pain after total knee replacement

AIM: To study the prevalence of persistent post-surgical pain(PPSP) and neuropathic pain(NP) after total knee replacement(TKR).METHODS: MEDLINE and Embase databases were searched for articles published until December 2014 in English language. Published articles were included if they referred to pain that lasts at least 3 mo after primary TKR for knee osteoarthritis, and measured pain with pain specific instruments. Studies that referred to pain caused by septic reasons and implant malalignment were excluded. Both prospective and retrospective studies were included and only 14 studies that match the inclusion criteria were selected for this review.RESULTS: The included studies were characterized by the heterogeneity on the scales used to measure pain and pre-operative factors related to PPSP and NP. The reported prevalence of PPSP and NP seems to be relatively high, but it varies among different studies. There is also evidence that the prevalence of post-surgical pain is related to the scale used for pain measurement. The prevalence of PPSP is ranging at 6 mo from 16% to 39% and at 12 mo from 13.1% to 23% and even 38% of the patients. The prevalence of NP at 6 mo post-operatively is ranging from 5.2% to13%. Pre-operative factors related to the development of PPSP also differ, including emotional functioning, such as depression and pain catastrophizing, number of comorbidities, pain problems elsewhere and operations in knees with early grade of osteoarthritis.CONCLUSION: No firm conclusions can be reached regarding the prevalence of PPSP and NP and the related factors due to the heterogeneity of the studies.

Persistent Post-Surgical Pain after Total Knee Arthroplasty at a Tertiary Care Hospital of a Low-Middle Income Country

Background: Persistent post-surgical pain (PPSP) is pain that lasts for 3 months or more after a surgical intervention, where other causes of pain have been excluded. There is scarce knowledge about the prevalence of PPSP in low- and middle-income countries (LMICs). The aim of our study was to assess the prevalence of PPSP after total knee arthroplasty (TKA) at our university hospital and explore factors associated with it. Methods: It was a prospective cross-sectional study. Approval was obtained from the Ethics Review Committee. Patients undergoing elective unilateral total knee arthroplasty under general or regional anaesthesia were recruited over a six months period. A designated pain nurse called the patients three months after surgery and asked about the presence of pain, its location, type, degree and associated factors. Patients who reported pain at three months were called a year after the surgery and the same questions were asked. Results: Eighty-two patients had TKA during the study period. At the time of discharge, 57 (69.5%) patients were satisfied with their postoperative pain management. Three months after the surgery, 13 (15.8%) patients reported pain. Pain was mild in 11 and moderate in two patients. At one-year follow-up, three patients (3.6%) reported pain that was mild to moderate in intensity. Pain disturbed sleep in all three patients and disturbed daily life routines in one patient. No significant difference was found in any of the variables when compared with patients who did not report pain at three months. Conclusions: Although PPSP is a recognized adverse outcome after TKA, little is known about its prevalence in LMICs. In our patient population, 15.8% reported pain three months after TKA, while at one year, 3.6% of patients reported mild to moderate pain. Multicenter studies are recommended for determining the overall prevalence in our patient population and for getting directions for making targeted efforts towards its prevention and treatment.

Comparing role of ATP between acute pain in neuromyelitis optica spectrum disorder and peripheral neuropathic pain

In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.

Lighting the shades of hidden pain:a role for spinal cord neurons and microglia in vestibulodynia

Vulvodynia,a chronic pain disorder affecting the vulvar region,represents a significant challenge in both diagnosis and treatment within the field of women’s health.This condition is characterized by chronic pain that significantly affects the quality of life of afflicted women.The present perspective paper examines the role of spinal sensitization and microglial activation in vulvodynia.

Effect of esketamine on reducing postpartum pain and depression

In this editorial,we comment on a recent article by Chen et al,that addressed the effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section.Poor management of postcesarean pain is associated with decreased maternal care for the baby,longer hospitalization,and higher risk of developing postpartum depression.Esketamine is a more potent S-enantiomer of ketamine which has shown promising analgesic and antidepressant properties for managing post-cesarean pain and depression in clinical studies.However,due to its potential adverse effects on the neurological and hemodynamic status of patients,it is recommended that its usage in low doses should be limited to cesarean candidates experiencing unbearable pain.Before any recommendation for routine perioperative use of esketamine,more standardized clinical trials are needed to strengthen our existing knowledge of its effectiveness in reducing postpartum pain and depression.

Application of virtual reality technology improves the functionality of brain networks in individuals experiencing pain

Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.

Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.

Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

Enhancing postoperative pain control by surgically-initiated rectus sheath block in abdominal aortic aneurysm open repair: A case report

BACKGROUND Abdominal aortic aneurysm(AAA)repair often involves significant postoperative pain,traditionally managed with systemic opioids,which can cause undesirable side effects.This case report explores the novel use of a surgically-initiated rectus sheath block with a catheter-over-needle assembly for pain management in AAA repair.CASE SUMMARY A 67-year-old female with hypertension and previous aortic dissection underwent elective open repair of an infrarenal AAA,which had grown from 3.4 cm to 4.3 cm over 14 months.A rectus sheath block was initiated surgically for postoperative pain control.The patient reported low pain scores and did not require systemic intravenous opioids,enabling early ambulation and discharge on postoperative day seven without complications.By preventing complications of systemic opi-oids,the method indicating a promising direction for postoperative pain management in major vascular surgeries.CONCLUSION Surgically-initiated rectus sheath block as a valuable tool for managing postoperative pain in AAA repair.

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.

重型创伤性脑损伤去骨瓣减压应用改良Paine点穿刺监测脑室内颅内压的优势

目的探讨重型创伤性脑损伤(TBI)开颅去骨瓣减压术(DC)中应用改良Paine点穿刺行脑室内颅内压(ICP)监测探头置入的优势。方法回顾性分析2020年4月-2022年4月嘉兴市第二医院收治的48例重型TBI患者的临床资料。所有患者均行DC联合脑室内ICP监护术,按照ICP监测术式的不同,分为观察组(23例)与对照组(25例),其中观察组行DC切口内改良Paine点穿刺脑室内ICP监测探头置入术,对照组行传统DC对侧切口颅骨钻孔经Kocher点脑室内ICP监测探头置入术。比较两组术前一般资料、手术用时、术后甘露醇使用剂量及持续时间、ICP监测持续时间、术后再出血率、颅内感染率、术后3个月时格拉斯哥预后评分(GOS)。结果两组一般资料、甘露醇使用剂量、甘露醇持续时间和ICP监测持续时间比较差异均无统计学意义(P>0.05);观察组手术用时、术后再出血率、颅内感染率明显少于或低于对照组(P<0.05);两组术后3个月GOS评分比较差异无统计学意义(P>0.05)。结论相较传统的DC对侧切口颅骨钻孔经Kocher点行脑室内ICP监测探头置入术,重型脑外伤DC术中通过切口内改良Paine点穿刺行脑室内ICP监测探头置入术可缩短手术用时,降低术后再出血率、颅内感染率。

Effect of ankle versus thigh tourniquets on post-operative pain in foot and ankle surgery

BACKGROUND Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss,improve visualization in the surgical field,and to potentially reduce surgical time.There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure,placement site,and duration of use.There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery.AIM To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery.METHODS Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken.Intraoperative tourniquet duration,tourniquet pressure and site,and postoperative pain scores using Visual Analogue Score were collected in immediate recovery,at six hours and at 24 h post-op.Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure,duration,site,and pain scores using Pearson correlation coefficient.RESULTS All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh.There was no correlation between the site of the tourniquet and pain scores in recovery,at six hours and after 24 h.There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op(r=0.14,P=0.04)but not at six or 24 h post-operatively.CONCLUSION This study shows that there was no statistically significant correlation between tourniquet pressure,site and postop pain in patients undergoing foot and ankle surgery.The choice of using a tourniquet is based on the surgeon's preference,with the goal of minimizing the duration of its application at the operative site.

Rehabilitation care for pain in elderly knee replacement patients

BACKGROUND Total knee arthroplasty(TKA)is recognized as the most effective surgical intervention for relieving pain and improving joint mobility and deformity in patients with knee osteoarthritis and other synovial diseases.The application of accelerated postoperative rehabilitation(enhanced recovery after surgery)has demonstrated its efficacy in improving patient outcomes,and early postoperative joint function exercise has become a key prognostic factor in knee replacement.The unexpected appearance of limb pain and swelling hindered the patient’s tendency for early mobilization,leading in prolonged hospitalization,delayed functional recovery and negative psychological responses.A retrospective analysis was conducted on a cohort of 116 patients who under-went TKA at our hospital between July 2019 and July 2021.The patients were divided into two groups:A control group(n=58)receiving programmatic nur-sing,and an observed group(n=58)receiving programmed nursing combined with a collaborative nursing model.A pain management team consisting of attending physicians,head nurses,and responsible nurses was established.Outcome measures included visual analogue scale(VAS)scores,activities of daily living(ADL)scale scores,and functional scores.The ADL scores of patients in both groups exhibited a continuous increase.However,there was no statistically significant difference in the ADL scores between the two groups at 48 h and the 7th d post-surgery(P>0.05).Upon reexamination at the 3rd mo,the observation group demonstrated higher ADL scores compared to the control group(67.48±14.69 vs 59.40±16.06,P<0.05).The VAS scores of both groups significantly decreased,with no significant difference observed between the groups at each time point(P>0.05).The functional status of patients in both groups exhibited a gradual increase prior to intervention and at the 1st,2nd,and 3rd month following discharge(P<0.05).There was no statistically significant difference in knee joint function scores between the two groups at the 1st month after discharge(47.52 vs 45.81,P>0.05).However,the knee joint function scores of patients in the observation group were significantly higher than those in the control group at the 2nd(59.38 vs 53.19,P<0.05)and 3rd month(71.92 vs 64.34,P<0.05)following discharge.CONCLUSION The utilization of programmed pain nursing in conjunction with collaborative nursing for out-of-hospital care of TKA patients has demonstrated favorable outcomes,encompassing pain reduction,enhanced prognosis,and improved nursing quality for patients.

Investigating epithelial-neuronal signaling contribution in visceral pain through colon organoid-dorsal root ganglion neuron co-cultures

Abdominal pain is a common symptom associated with irritable bowel syndrome and inflammatory bowel diseases(IBDs),affecting about 20%of the global population(Grundy et al.,2019).Current pain therapies are poorly effective on visceral pain of intestinal origin and present several side effects,hence the need to identify novel molecular and cellular targets for drug development.

Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain

Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.

Meta-analysis of factors influencing anterior knee pain after total knee arthroplasty

BACKGROUND Total knee arthroplasty(TKA)is a mature procedure recommended for correcting knee osteoarthritis deformity,relieving pain,and restoring normal biomechanics.Although TKA is a successful and cost-effective procedure,patient dissatisfaction is as high as 50%.Knee pain after TKA is a significant cause of patient dissatisfaction;the most common location for residual pain is the anterior region.Between 4%and 40%of patients have anterior knee pain(AKP).AIM To investigate the effect of various TKA procedures on postoperative AKP.METHODS We searched PubMed,EMBASE,and Cochrane from January 2000 to September 2022.Randomized controlled trials with one intervention in the experimental group and no corresponding intervention(or other interventions)in the control group were collected.Two researchers independently read the title and abstract of the studies,preliminarily screened the articles,and read the full text in detail according to the selection criteria.Conflicts were resolved by consultation with a third researcher.And relevant data from the included studies were extracted and analyzed using Review Manager 5.4 software.RESULTS There were 25 randomized controlled trials;13 were comparative studies with or without patellar resurfacing.The meta-analysis showed no significant difference between the experimental and control groups(P=0.61).Six studies were comparative studies of circumpatellar denervation vs non-denervation,divided into three subgroups for meta-analysis.The two-subgroup meta-analysis showed no significant difference between the experimental and the control groups(P=0.31,P=0.50).One subgroup meta-analysis showed a significant difference between the experimental and control groups(P=0.001).Two studies compared fixed-bearing TKA and mobile-bearing TKA;the results meta-analysis showed no significant difference between the experimental and control groups(P=0.630).Two studies compared lateral retinacular release vs non-release;the meta-analysis showed a significant difference between the experimental and control groups(P=0.002);two other studies compared other factors.CONCLUSION Patellar resurfacing,mobile-bearing TKA,and fixed-bearing TKA do not reduce the incidence of AKP.Lateral retinacular release can reduce AKP;however,whether circumpatellar denervation can reduce AKP is controversial.

Relationship between Kawasaki disease and abdominal pain

This editorial presents an analysis of an article recently published in the World Journal of Clinical Cases.Kawasaki disease(KD)is a well-known pediatric vasculitis characterized by fever,rash,conjunctivitis,oral mucosal changes,and swelling of the extremities.This editorial aims to delve into the intricate relationship between KD and abdominal pain,drawing insights from recent research findings to provide a comprehensive understanding and potential avenues for future investigation.

Antimicrobial approach of abdominal post-surgical infections

Abdominal surgical site infections(SSIs)are infections that occur after abdominal surgery.They can be superficial,involving the skin tissue only,or more profound,involving deeper skin tissues including organs and implanted materials.Currently,SSIs are large global health problem with an incidence that varies significantly depending on the United Nations’Human Development Index.The purpose of this review is to provide a practical update on the latest available literature on SSIs,focusing on causative pathogens and treatment with an overview of the ongoing studies of new therapeutic strategies.

Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

Interventional pain therapy in cervical post-surgery syndrome

Fifteen percent to forty percent of patients present with persistent disabling neck pain or radicular pain after cervical spine surgery. Persistent pain after cervical surgery is called cervical post-surgery syndrome(CPSS). This review investigates the literature about interventional pain therapy for these patients. Because different interventions with different anatomical targets exist, it is important to find the possible pain source. There has to be a distinction between radicular symptoms(radicular pain or radiculopathy) or axial pain(neck pain) and between persistent pain and a new onset of pain after surgery. In the case of radicular symptoms, inadequate decompression or nerve root adherence because of perineural scarring are possible pain causes. Multiple structures in the cervical spine are able to cause neck pain. Hereby, the type of surgery and also the number of segments treated is relevant. After fusion surgery, the so-called adjacent level syndrome is a possible pain source. After arthroplasty, the load of the facet joints in the index segment increases and can cause pain. Further, degenerative alterations progress. In general, two fundamentally different therapeutic approaches for interventional pain therapy for the cervical spine exist: Treatment of facet joint pain with radiofrequency denervation or facet nerve blocks, and epidural injections either via a transforaminal or via an interlaminar approach. The literature about interventions in CPSS is limited to single studies with a small number of patients. However, some evidence exists for these procedures. Interventional pain therapies are eligible as a target-specific therapy option. However, the risk of theses procedures(especially transforaminal epidural injections) must be weighed against the benefit.